We will use a specialized system to model human immune responses. Using mice that have no immune system of their own, we will reconstitute a human-like immune system from stem cells isolated from cord blood samples. These cells will create a human immune system in the mice; the mice can then be vaccinated and antigen-specific T cells can be monitored for their responses. In particular, we are interested in how CD8 T cells develop in the presence of high or low levels of antigen. We have seen in other models that different levels of antigen can lead to very different types of immune responses; in general, low antigen exposure generates T cells that are more highly functional and capable of protection. However, the mechanism for this is unknown and not amenable to exploration except in highly defined systems. This humanized mouse model will give us a highly defined, reproducible system for determining how different types of immune responses can be generated following vaccination.